The Status of
            <i>In Vitro</i>
            Toxicity Studies in The Risk Assessment of Nanomaterials

Park, Margriet Vdz; Lankveld, D. P. K.; Loveren, Henk Van; Jong, Wim H. de

doi:10.2217/nnm.09.40

Cited by 98 publications

(47 citation statements)

References 68 publications

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“…Surprisingly, this fact has received little attention in the literature, where the focus seems to be predominately on the suitability of assays, cell types, and methods of characterization (Doak et al, 2009;Donaldson et al, 2009;Kroll et al, 2009;Marquis et al, 2009;Park et al, 2009;Stone et al, 2009) A successful dosimetry paradigm for nanotoxicology or nanobiology should parallel the widely accepted and applied paradigm for particles in-vivo, and should reflect certain core attributes; a focus on dose to the cell, adequate characterization of the particles, and represent the mode of action under study. These core attributes ensure that the operating paradigm for nanomaterial dosimetry support accuracy, scalability and interpretability of all in-vitro nanomaterial research.…”

Section: Submerged Cell Exposure Systemsmentioning

confidence: 99%

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology

Paur

Cassee

Teeguarden

et al. 2011

Journal of Aerosol Science

274

223

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Section: Submerged Cell Exposure Systemsmentioning

confidence: 99%

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology

Paur

Cassee

Teeguarden

et al. 2011

Journal of Aerosol Science

274

223

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“…Furthermore, it is known that NMs may interfere with the read out system of in vitro assays by, eg, light absorbance and/or autofluorescence. 126,127 Therefore, potential assay interference by the investigational NMPs needs to be carefully evaluated when using in vitro assays for hazard identification in the testing strategy.…”

Section: Recommendations For Immunotoxicity Testing Of Nmpsmentioning

confidence: 99%

A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

Giannakou¹,

Park²,

Jong³

et al. 2016

IJN

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Nanomaterials (NMs) are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs) currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome activation, and hypersensitivity, are not readily detected by using current testing guidelines. Immunotoxicity of NMPs would be more accurately evaluated by an expanded testing strategy that is equipped to stratify applicable testing for the various types of NMPs.

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“…It has generally been assumed that in vitro toxicity tests designed for soluble chemicals are appropriate for nanomaterials. However extrapolation of in vitro toxicology findings to humans is not so obvious when the mode of action and/or metabolic conditions in the cell culture model may not be relevant in humans [496][497][498]. This is not an easy task, since the standardized established tests should work for multiple particle types, despite the fact that these NPs have different characteristics and behaviors (fluorescence, magnetism, metallic nature…) but it should definitely be undertaken.…”

Section: Reaction Typementioning

confidence: 99%

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

Trequesser¹,

Seznec²,

Delville³

2016

Nano Online

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The successful development of nanomaterials illustrates the considerable interest in the development of new molecular probes for medical diagnosis and imaging. Substantial progress was made in synthesis protocol and characterization of these materials whereas toxicological issues are sometimes incomplete. Nanoparticle-based contrast agents tend to become efficient tools for enhancing medical diagnostics and surgery for a wide range of 2 imaging modalities. Multimodal nanoparticles (NPs) are much more efficient than conventional molecular-scale contrast agents. They provide new abilities for in vivo detection and enhanced targeting efficiencies through longer circulation times, designed clearance pathways, and multiple binding capacities. Properly protected, they can safely be used for the fabrication of various functional systems with targeting properties, reduced toxicity and proper removal from the body. This review mainly describes the advances in the development of mono-to multimodal NPs and their in vitro and in vivo relevant biomedical applications ranging from imaging and tracking to cancer treatment. Besides specific applications for classical imaging, (MRI, PET, CT, US, PAI) are also mentioned less common imaging techniques such as terahertz molecular imaging (THMI) or ion beam analysis (IBA).Perspectives on multimodal theranostic NPs and their potential for clinical advances are also mentioned.

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The Status of In Vitro Toxicity Studies in The Risk Assessment of Nanomaterials

Cited by 98 publications

References 68 publications

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology

A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

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